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Table 1 Characteristics of included studies

From: Patient reported outcome instruments used in clinical trials of HIV-infected adults on NNRTI-based therapy: a 10-year review

Study reference Population characteristics1 Study design Objective Treatment groups PRO instruments2(validated, not validated) Types of PRO instruments (validated only)
Dabaghzadeh (2013) [7] No prior EFV treatment experience (n = 51) RCT (double-blind, placebo-controlled) To assess the effect of cyproheptadine in prevention of neuropsychiatric adverse adverse drug reactions of ARV regimens containing EFV 1) ARV therapy (including EFV) + cyproheptadine BDI-II Psychiatric symptoms (3)
HAM-D Depression (2)
2) ARV therapy (including EFV) + placebo PANSS Anxiety (1)
PANSI Sleep (1)
SCL-90 somatization subscale
Bucciardini (2012) [8] Treatment-experienced patients with treatment failure, resistance, or intolerance with HAART (2 NRTIs + NNRTI or PI) (n = 101) Prospective, observational study (sub-set of ISS-NIA study) To evaluate rates and determinants of virological failure in triple-class experienced patients receiving raltegravir-based regimens 1) All patients received RAL-based therapy; study compared patients with and without virologic failure on RAL ISSQoL HRQL: General (1)
Lake (2012) [9] HIV-infected women with central adiposity and viral suppression on NNRTI- or PI-based HAART (n = 37) RCT (open-label) To evaluate effects of a switch from a PI or NNRTI to RAL on adipose tissue volume and metabolic changes 1) Immediate switch of PI or NNRTI to RAL (continuing prior NRTI backbone) CES-D Depression (1)
Body Image Impact scale Psychiatric symptoms (1)
2) Delayed switch (at 24 weeks) of PI or NNRTI to RAL (continuing prior NRTI backbone)
Mosam (2012) [10] Treatment-naïve patients with HIV-associated Kaposi sarcoma (n = 112) RCT (open-label) To compare HRQL between 2 ARV regimens: ZDV/3TC/NFV versus ZDV/3TC/NVP 1) d4T/3TC/NVP EORTC QLQ-30 HRQL: General (1)
2) d4T/3TC/NVP + chemotherapy
Cooper (2011) [11] Treatment-experienced patients on stable ZDV/3TC/EFV regimen (n = 234) RCT (open-label) To assess the effect of switching ZDV/3TC/EFV to TDF/FTC/EFV on adherence, beliefs about ARV therapy and HQRL 1) Continue ZDV/3TC/EFV twice daily BMQ-ART HRQL: General (1)
HAART Intrusiveness Scale Medication beliefs: HIV-targeted (2)
2) Switch to TDF/FTC/EFV once daily SF-12 (v2)
Nguyen (2011) [12] Stable EFV-containing HAART regimen (n = 53) RCT (double-blind, cross-over) To investigate the effect of replacing EFV with RAL on patient preference, sleep quality, daytime sleepiness, anxiety, and lipid levels 1) Continue EFV-containing regimen, then switch EFV to RAL (continuing prior NRTI backbone) ESS Sleep (3)
2) RAL + prior NRTI backbone, then switch RAL to EFV (continue prior NRTI backbone) Treatment preference
Treatment satisfaction
Nguyen (2011) [13] Stable EFV-containing HAART regimen (n = 58) RCT (double-blind, cross-over) To investigate the effect of replacing EFV with ETR on patient preference, sleep, anxiety, and lipid levels 1) EFV-based therapy ESS Sleep (3)
2) ETR-based therapy SSS Anxiety/depression/stress (1)
Treatment preference
Treatment satisfaction
Campo (2010) [14] PI-based HAART regimen without history of virological failure (n = 262) RCT (open-label) To evaluate the efficacy, safety and PROs of regimen switching to EFV-based HAART 1) Switch to EFV/3TC/ddI FAHI HRQL: HIV (1)
2) Switch PI to EFV (continuing prior NRTIs) IIRS HRQL: General chronic disease (1)
Treatment preference
Treatment satisfaction
Cella (2010) [15] Stable, but virologically failing ARV regimen (n = 1,203) RCT (pooled analysis of DUET-1 and DUET-2) To study the effects of etravirine versus placebo on the HRQL of HIV-infected patients 1) ETR 200 mg twice-daily3 FAHI HRQL: HIV (1)
2) Placebo3
Cooper (2010)] [16] HIV-infected, treatment-naïve patients (n = 87) RCT (open-label) To determine the impact of once-nightly versus twice-daily dosing and beliefs about HAART on adherence to EFV-based HAART in ARV-naïve patients 1) ddI/3TC/EFV once nightly BMQ-ART Medication beliefs: HIV-targeted (2)
2) AZT/3TC twice daily + EFV nightly HAART Intrusiveness Scale
Cooper (2010) [17]; Regnault (2009) [18] HIV-infected treatment-naïve patients (n = 895) RCT (double-blind) [MERIT] To evaluate the long-term efficacy, safety, adherence, and HRQL of once-daily EFV-based HAART 1) ZDV/3TC + MVC 300 mg twice daily HIV-SI/SDM HIV symptoms (1)
2) ZDV/3TC + MVC 600 mg once daily
3) ZDV/3TC + EFV 600 mg once daily
Hodder (2010) [19]; DeJesus (2009) [20] PI- or NNRTI-based ARV regimen with virologic suppression (n = 300) RCT (open-label) To evaluate the therapeutic switch to a single-tablet formulation of EFV/FTC/TDF among virologically suppressed, HIV-infected adults 1) EFV/FTC/TDF SF-36 (v2) HRQL: General (1)
2) Continue baseline ARVs (PI- or NNRTI-based) HIV-SI/SDM HIV symptoms (1)
Treatmet preference
Perceived ease of regimen
Potard (2010) [21] Treatment experienced, NNRTI-naïve (n = 239) Prospective, observational study To assess changes in HRQL after switching to an NNRTI-containing regimen 1) EFV-based therapy HADS Anxiety/depression (1)
2) NVP-based therapy HIV-SI/SDM
WHOQOL-HIV HIV symptoms (1)
BREF HRQL: General (2)
SF-12 (v2)
Clifford (2009) [22] Treatment-naïve; study reports long-term follow-up of patients after unblinding of the AZT/3TC/ABC treatment arm (n = 303) RCT (secondary analysis of A5095) To evaluate the long-term impact of EFV-based regimens on neuropsychological performance 1) AZT/3TC/EFV CES-D Depression (1)
2) AZT/3TC/ABC PSQI Sleep (1)
STAI Anxiety (1)
Neuropsychiatric symptoms
Gutierrez-Valencia (2009) [23] Patients scheduled to receive an EFV-containing treatment plus 2 NRTIs (n = 114) RCT (double-blind) To determine if starting EFV in a stepwise dose schedule decreases EFV-related neuropsychiatric adverse events while maintaining efficacy 1) EFV-based therapy (stepwise dosing) OSQ Sleep (1)
2) EFV-based therapy (full dose) Neuropsychiatric symptoms
Jayaweera (2009 ) [24] Treatment-experienced patients (n = 65) Prospective, single-arm trial (open-label) [DART I] To evaluate the long-term efficacy, safety, adherence, and HRQL of once-daily EFV-based HAART 1) ddI/3TC/EFV once-daily MOS-HIV HRQL: HIV (1)
Jayaweera (2009) [24] Treatment-experienced patients (n = 70) Prospective, single-arm trial (open-label) [DART II] To evaluate the long-term efficacy, safety, adherence, and HRQL of once-daily EFV-based HAART 1) d4T/3TC/EFV once-daily MOS-HIV HRQL: HIV (1)
Boyle (2008) [25] Treatment-experienced patients on stable twice-daily or more frequent HAART (n = 320) RCT (open-label) To evaluate the effect of regimen simplification on maintenance of virologic suppression and treatment adherence 1) Continue baseline ARVs (BID + dosing) FAHI HRQL: HIV (1)
IIRS HRQL: General (1)
2) Switch to once-daily d4T/3TC/EFV Treatment preference
Treatment satisfaction
DeJesus (2008) [26] Stable regimen of fixed-dose AZT/3TC with EFV, experiencing AZT/3TC-related adverse effects or who might benefit from a simplified regimen (n = 402) Prospective, single-arm trial To evaluate the impact of switching from twice-daily AZT/3TC to once-daily TDF/FTC with EFV) 1) Switch from twice-daily AZT/3TC to once-daily TDF/FTC with EFV SF-36 (v2) HRQL: General (1)
HIV-SI/SDM HIV symptoms (1)
Treatment satisfaction
Bucciardini (2007) [27] Treatment-naïve (n = 139) RCT (secondary analysis of INITIO-QoL data) To detect differences in patient’s HRQL among the 3 study treatment groups in the INITIO trial 1) ddI/d4T/EFV MOS-HIV HRQL: HIV (1)
2) ddI/d4T/NFV
3) ddI/d4T/EFV/NFV
Lafaurie (2008) [28] NNRTI-naïve, receiving stable HAART consisting of at least 1 PI, 1 NRTI and AZT (n = 158) RCT (open-label; secondary analysis of ALIZE data) To assess if patients who have tolerated long-term AZT regimens will benefit from a switch to EFV/ddI/FTC 1) Maintenance of stable PI-containing regimen MOS-HIV HRQL: HIV (1)
2) Switch to once-daily EFV/ddI/FTC
Journot (2006) [29] NNRTI-naïve, receiving unchanged HAART for ≥6 months consisting of at least 1 PI and 2 NRTIs (n = 355) RCT (open-label; secondary analysis of ALIZE data) To determine whether EFV use is associated with a higher incidence of depressive disorders compared to PI-containing regimens 1) Continue PI-based therapy CES-D Depression (1)
2) Switch to EFV-based therapy
Portsmouth (2005) [30] Treatment-experienced patients with virologic suppression receiving d4T/3TC/EFV or ZDV/3TC/EFV (n = 43) RCT (open-label) To assess whether virologically controlled HIV-1-infected individuals switched from a twice-daily antiretroviral regimen to a once-daily regimen demonstrate improved adherence and quality of life while maintaining virological control 1) Continue twice-daily regimen of d4T(IR)/3TC/EFV or ZDV/3TC/EFV MOS-HIV HRQL: HIV (1)
2) Switch to once-daily d4T(PRC)/3TC/EFV
Casado (2004) [31] Treatment-naïve; subset of patients with HRQL data in original COMBINE trial (n = 127) RCT (secondary analysis of COMBINE) To compare HRQL between 2 ARV regimens: ZDV/3TC/NFV versus ZDV/3TC/NVP 1) ZDV/3TC/NFV MOS-HIV HRQL: HIV (1)
Negredo (2004) [32] HAART experienced patients with long-lasting viral suppression (n = 169) Prospective, observational study To explore the long-term safety, and the virological and immunological efficacy of once-daily ddI/TDF/NVP in previously HAART-experienced subjects with long-lasting viral suppression 1) Continue twice-daily ARV therapy (PI- or NNRTI-based) MOS-HIV HRQL: HIV (1)
2) Switch to once-daily ddI/TDF/NVP
van Leth (2004) [33] Treatment-naïve; subset of patients with HRQL data in original 2NN clinical trial (n = 917) RCT (secondary analysis of 2NN data) To investigate whether these differences in the safety profiles of EFV and NVP translates into differences in HRQL 1) d4T/3TC/EFV MOS-HIV HRQL: HIV (1)
2) d4T/3TC/NVP
3) d4T/3TC/EFV/NVP
  1. Abbreviations: 3TC lamivudine, ABC abacavir, ACTG AIDS Clinical Trials Group, ARV antiretroviral, AZT zidovudine, BDI-II Beck Depression Inventory, second edition, BMQ-ART Beliefs about Medicines Questionnaire, adapted for antiretroviral therapy, CES-D Centre for Epidemiologic Studies-Depression scale, d4T stavudine, DASS21 Depression Anxiety and Stress Scale-short version, ddI didanosine, EFV efavirenz, EORTC QLQ-30 European Organization for Research and Treatment of Cancer Quality of Lfe Questionnaire, ESS Epworth Sleep Score, ETR etravirine, FAHI Functional Assessment of HIV Infection, FTC emtricitabine, GSQS Groningen Sleep Quality Score, HAART highly-active antiretroviral therapy, HADS Hospital Anxiety and Depression Scale, HAM-A Hamilton Anxiety Rating Scale, HAM-D Hamilton Depression Rating Scale, HIV-SI HIV Symptom Index, HRQL health-related quality of life, IIRS Illness Intrusiveness Rating Scale, ISSQoL Istituto Superiore di Sanità Quality of Life, MOS-HIV Medical Outcomes Study HIV health survey, NFV nelfinavir, NNRTI non-nucleoside reverse transcriptase inhibitor, NRTI nucleoside/nucleotide reverse transcriptase inhibitor, NVP nevirapine, PANSI Positive and Negative Syndrome Scale, PANSS Positive and Negative Suicide Ideation, PI protease inhibitor, PRO patient-reported outcome, PSQI Pittsburgh Sleep Quality Index, RCT randomized controlled trial, SCL-90 Symptom Checklist-90, SDM Symptom Distress Module, SF-12 MOS 12-item short-form health survey, SF-36 MOS 36-item short-form health survey, SSS Stanford Sleepiness Scale, STAI State-Trait Anxiety Inventory, TDF tenofovir, WHOQOL-HIV BREF World Health Organization Quality of Life-HIV, short version.
  2. 1All subjects are HIV-infected adults; 2Excludes patient-reported adherence-only instruments (e.g., ACTG Adherence Questionnaire); 3Both groups received darunavir/ritonavir (DRV/r) and an investigator-selected optimized background regimen of at least 2 ARVs consisting of NRTI(s).